Current Pharmaceutical Design - Volume 18, Issue 7, 2012

Sigma (σ ) receptor history started in 1976 when Martin et al. proposed the σ opioid receptors (“ σ-opioid”) to account for the psychotomimetic effects that the benzomorphan SKF-10,047 (N-allylnormetazocine) caused in the chronic spinal dog model and which were blocked by the opioid antagonist naloxone [1]. Later Su et al. identified a binding site which was labeled by [3H]-SKF-10,047 [2] but which was insensitive to na Read More

The σ receptors are regarded as unique binding sites, distinct from opiate and PCP receptors and implicated in higher brain function. They were classified into l and 2 subtypes, the former was cloned from rodent and human tissues while the latter has not yet been fully characterized. Although the precise mechanism of the functional response of receptors is still uncertain, it has been accepted that they can modulate a Read More

Cognitive impairment is a core feature of patients with neuropsychiatric diseases such as schizophrenia and psychotic depression. The drugs currently used to treat cognitive impairment have significant limitations, ensuring that the search for more effective therapies remains active. Endoplasmic reticulum protein sigma-1 receptors are unique binding sites in the brain that exert a potent effect on multiple neurotrans Read More

Since their proposal in 1976, sigma (σ) receptors have been increasingly implicated in the pathophysiology of virtually all major central nervous system (CNS) disorders, including anxiety, depression, schizophrenia, and drug addiction. Due to their involvement in motor function and higher cognitive function,σ receptors have also been implicated in movement disorders (such as Parkinson's disease) and memory deficits (incl Read More

Drug abuse is currently a large economic and societal burden in countries around the globe. Many drugs of abuse currently lack adequate therapies aimed at treating both the addiction and negative complications often associated with their use. Sigma-1 receptors were discovered over 30 years ago and have recently become targets for the development of pharmacotherapies aimed at treating substance abuse and add Read More

The sigma-1 receptor is a 26 kDa endoplasmic reticulum resident membrane protein that has been shown to have chaperone activity in addition to its promiscuous binding to pharmacological agents. Ligand binding domain(s) of the sigma-1 receptor have been identified using the E. coli expressed and purified receptor protein and novel radioiodinated azido photoaffinity probes followed by proteolytic and chemical cleava Read More

The existing pharmacophore models for 1 receptor ligands are summarized. A common feature of these models is a basic amino group surrounded by different hydrophobic structural elements. The development of novel spirocyclic 1 receptor ligands (e.g. 3, 4) is based on these models. Enlargement of the distance between the basic amino group and the “Primary Hydrophobic Region ” by attachment of the amino group Read More

Although several pieces of information are still missing about sigma-2 ( 2) receptor, the production of high affinity 2 receptor ligands allowed important acquisitions. Morphans such as CB64D and CB184 were the first truly 2-selective ligands synthesized, and their use in cell cultures highlighted the relationship between 2 receptors and cell proliferation, shedding light on important diagnostic and therapeutic potentials Read More

The renin-angiotensin-aldosterone system (RAAS) exerts a crucial role in the regulation of blood pressure and its pharmacological inhibition is essential to prevent cardiovascular events related to hypertension [1]. This “historical” concept has been recently updated by several knowledge improvements, suggesting that the RAAS might induce a series of “pleiotropic activities” [2]. This system has been shown to trigger intra Read More

The renin angiotensin aldosterone system (RAAS) inhibitors induce an incomplete blockade of the system at different steps. Recently, the dual RAAS therapy is emerging in clinical practice, although there is a lack of evidence on safety and efficacy for this combination in several cardiovascular diseases. In this review, we evaluated the advantages and disadvantages of dual RAAS blockade in hypertension, proteinuric renal disea Read More

ACE inhibitors have established their role in the management of hypertension as well as in the primary and secondary prevention of cardiovascular events. Furthermore, they have proven their role in delaying the worsening of renal function in patients with chronic renal disease. Over the last few years their use to prevent the new onset of diabetes has come to the forefront. Post-hoc analyses of large mutli-center clinical trials Read More

Recent data support the idea that the effects of RAS are not restricted to the cardiovascular and renal systems. Importantly, RAS modulates free radical production and the cellular synthesis of several molecules such as cytokines, chemokines and transcription factors. These functions reflect directly the RAS ability to modulate the cell growth, senescence and migration. Activation of the classic RAS, ACE/Ang II/AT1R, has been Read More

Chronic kidney disease has become a major public health problem worldwide mainly as a consequence of the emerging epidemic of hypertension, diabetes, and obesity. It is currently estimated that nearly 15% of the general population has some degree of renal damage, a figure that reaches 50% in at-risk subgroups. Renin-angiotensin-aldosterone system (RAAS) inhibitors represent the agents of choice to control hypertension Read More

Renin-Angiotensin-Aldosterone (RAAS) is a hormone system which acts on multiple physiologic pathways primarily by regulating blood pressure and fluid balance, but also by local autocrine and paracrine actions. In pathophysiologic conditions RAAS also contributes to the development of atherosclerosis and its various manifestations, both directly and indirectly through the actions on other systems. RAAS mainly acts as a p Read More

Despite the attractiveness of a vaccination strategy for the treatment of high blood pressure, and many decades of research, attempts to translate this strategy to hypertension management have been unsuccessful. Immunization against components of the renin angiotensin system offers the prospect of improved long-term control of hypertension because efficacy does not require daily compliance with oral medication. Moreo Read More

Guidelines for the treatment of hypertension allow a wide range of choices to the physicians; however some differences are present about the preferred drugs to start treatment. The most important aim remains an adequate decrease of blood pressure, something not perfectly obtained in the general population, but some classes of anti-hypertensive drugs could show protective effects on cardiovascular events, which are i Read More